São Paulo (SP), a densely populated state in southeast Brazil that contains one of the world's largest urban regions, has experienced its largest yellow fever virus (YFV) outbreak in decades. Surveillance in non-human primates (NHP) is important in order to detect YFV early during an epidemic or epizootic, to quantify the magnitude of the outbreak in NHP, and to evaluate the risk of YFV spillover infection in human populations.

To better understand the genetic diversity and spatial distribution of YFV during the current outbreak in southeast Brazil, we generated 46 new virus genomes from YFV positive cases identified in 18 different municipalities in SP, mostly sampled from non-human primates between April 2017 and February 2018.

Our data show that most NHP cases in São Paulo state were likely caused by the introduction of a single YFV lineage from Minas Gerais to São Paulo. Phylogenetic and phylogeographic analyses of these data indicate that YFV spread southwards from Minas Gerais into São Paulo state at a typical rate of <1km per day.

These results shed light in the sylvatic transmission of yellow fever in highly fragmented forested regions in São Paulo state and highlight the importance of continued operational research and surveillance of zoonotic pathogens in sentinel populations.

April 18, 2019

In Brazil, seasonal increases of yellow fever have historically occurred between December and May. During the 2016-2017 and 2017-2018 seasons, the number of yellow fever cases was much larger than in previous years (Figures 1 & 2). The increase in cases was partly due to a geographical expansion of the areas affected by yellow fever to include areas previously considered risk-free (Figure 3).

In the current 2018- 2019 season (July 2018 to March 2019), a total of 75 confirmed human cases, including 17 deaths (case fatality rate = 23%), have been reported in Brazil in the states of São Paulo (62), Paraná (12), and Santa Catarina (1). Of these cases, 88% (66/75) are males, the median age is 43 years, and 71% (53/75) are rural workers.

Likewise, in the same reporting period of July 2018 to March 2019, 33 confirmed epizootics were reported in five federal states: São Paulo (20), Rio de Janeiro (8), Minas Gerais (1), Mato Grosso (2), and Paraná (2). In the four weeks preceding this report, epizootics have been confirmed in São Paulo and Paraná states.

Brazil is currently in the period historically recognized as having the highest transmission (seasonal period), which occurs between December and May. The expansion of the historical area of yellow fever transmission to areas previously considered risk-free led to two waves of transmission (Figure 1), one during the 2016-2017 seasonal period, with 778 confirmed human cases, including 262 deaths, and another during the 2017-2018 seasonal period, with 1,376 confirmed human cases, including 483 deaths.

In the current seasonal period (2018-2019), 50 confirmed human cases, including 12 deaths, have been reported in the states of São Paulo (46 cases) and Paraná (4 cases). In São Paulo, the municipalities considered as probable sites of infection are: Eldorado (15 cases), Iporanga (12 cases), Cananeia (4 cases), Cajati (3 cases), Barra do Turbo (2 cases), Jacupiranga (2 cases), Caraguatatuba (1 case), Registro (1 case), Pariquera-açu (1 case), Serra Negra (1 case), Sete Barras (1 case), Juquiá (1 case), Vargem (1 case), and the probable site of infection for 1 case remains under investigation. With the exception of Serra Negra, Vargem (bordering the state of Minas Gerais), and Caraguatatuba, the rest of the municipalities are in the southern part of the state of São Paulo.

The probable sites of infection for the 4 confirmed cases in the state of Paraná are Guaraqueçaba (2 cases) and Adrianópolis (2 cases) municipalities.

Among confirmed cases, 90% (45/50) are male and the median age is 43 years (range 18 to 87 years). All of the deaths occurred among confirmed cases in the state of São Paulo.

To date, the number of human cases reported during the current 2018-2019 seasonal period is substantially lower than observed during the two previous seasonal periods, when the number of cases surpassed that which was reported in several decades. Nonetheless, the occurrence of cases and epizootics in the southern part of the state of São Paulo and in the state of Paraná indicates the progression of transmission towards the Southeast and South regions of the country (Figure 2), with the possibility of reaching bordering countries such as Argentina and Paraguay.

In the 2018-2019 seasonal period, most of the confirmed epizootics (90%) were reported in the Southeast Region of the country (27/30). In epidemiological week (EW) 4 of 2019, a confirmed epizootic was also reported in the South Region in the state of Paraná, in areas where yellow fever virus circulation was not detected since the re-emergence of the virus in 2014.

February 12, 2019

Brazil is currently in the seasonal period for yellow fever, which occurs from December through May. The expansion of the historical area of yellow fever transmission to areas in the south-east of the country in areas along the Atlantic coast previously considered risk-free led to two waves of transmission (Figure 1). One during the 2016–2017 seasonal period, with 778 human cases, including 262 deaths, and another during the 2017–2018 seasonal period, with 1376 human cases, including 483 deaths.

From December 2018 through January 2019, 361 confirmed human cases, including eight deaths, have been reported in 11 municipalities of two states of Brazil. In the southern part of São Paulo state, seven municipalities:El dorado (16 cases), Jacupiranga (1 case), Iporanga (7 cases), Cananeia (3 cases), Cajati (2), Pariquera-Açu (1), and Sete Barras (1) reported confirmed cases. In the same state, additional cases in Vargem (1) and Serra Negra (1) municipalities were confirmed on the border with Minas Gerais State. Additionally, two cases have been confirmed in the municipalities of Antonina and Adrianópolis, located in the eastern part of Paraná State. These are the first confirmed yellow fever cases reported since 2015 from Paraná, a populous state with an international border. Among these confirmed cases, 89% (32/36) are male, the median age is 43 years, and at least 64% (23/36) are rural workers.

Human cases reported so far during the current 2018–2019 period (July 2018 to Jan 2019) in nine municipalities in São Paulo State, as well as the confirmation of human cases and epizootic due to yellow fever in the state of Paraná, mark the beginning of what could be a third wave and a progression of the outbreak towards the Southeast and South regions of the country (Figure 2).

While too early to determine if this year will show the high numbers of human cases observed in the last two large seasonal peaks, there is indication that the virus transmission is continuing to spread in a southerly direction and in areas with low population immunity.

January 16, 2019

The Kwara State Government has confirmed two cases of Lassa Fever infecting a husband and wife in the state.

The government also confirmed an outbreak of circulating Vaccine Derived Polio Virus which claimed the life of a two-year-old girl and a case of Yellow Fever infecting a farmer.

Speaking with newsmen on Tuesday during at a news briefing, the Kwara Commissioner for Health, Alhaji Usman Rifun-Kolo said the outbreak of Lassa Fever was identified in a farm settlement in Taberu, Baruten Local Government Area.

He, however, explained that the two cases of the disease affected a husband and wife, who were natives of Benin Republic, which shares a border with the state. He added that the husband and wife are farming in Baruten.

“These cases of Lassa Fever originated from Benin Republic, whose citizen have inter-relations with people in Baruten area,” he said.

According to him, the husband and wife were diagnosed in a health facility, and that the state government had already deployed disease surveillance team to identify those who have been in contact with the patients.

Rifun-Kolo further explained that the surveillance team identified four people with history of fever in the area.

He said that the four cases raised suspicion of Lassa fever, which prompted them to take samples from the individuals for further investigation.

January 09, 2019

LONDON, Jan 8 (Thomson Reuters Foundation) - Scientists in the United States said on Tuesday they had taken a major step toward developing a "mosquito birth control" drug to curb the spread of malaria and other killer diseases blamed for hundreds of thousands of deaths a year.

Researchers at the University of Arizona said they had discovered a protein unique to female mosquitoes which is critical for their young to hatch.

When the scientists blocked the protein, the females laid eggs with defective shells causing the embryos inside to die.

The team said developing drugs which targetted the protein could provide a way to reduce mosquito populations without harming beneficial insects such as bees.

"It's an important discovery," Roger Miesfeld, head of the university's department of chemistry and biochemistry, told the Thomson Reuters Foundation by phone.

"We're certainly excited about it ... This gets around mosquito resistance and also has a much better chance of being bio-safe (than other methods)."

Mosquitoes are one of the world's deadliest animals, according to the World Health Organization (WHO) which has warned that global progress against malaria is stalling.

The disease infected around 216 million people in 2016, killing 445,000 of them, predominantly babies and young children in sub-Saharan Africa.

Other diseases spread by mosquitoes include Zika, Chikungunya, yellow fever, West Nile virus and dengue, which has risen 30-fold in recent decades, according to the WHO.

Miesfeld said current methods of controlling mosquitoes had been used for so long that the insects were becoming resistant.

He said the research team was surprised to find that treated females could no longer reproduce for the rest of their two- to three-week life span.

"Once we knock down this protein she (the mosquito) no longer makes viable eggs even after multiple blood feedings so ... birth control is a great way to describe it."

He said he hoped the discovery could lead to the development of a new generation of insecticides in five years.

These could be applied to bed nets and other areas in the same way as current sprays and would be absorbed by the mosquito through her legs and body.

On 22 November 2018, the World Health Organization was informed of a cluster of suspected Yellow fever (YF) cases and deaths in Edo State, Nigeria. Edo State is located less than 400km from Lagos on a dense population movement axis between Lagos and South-Eastern Nigeria. Edo State is also a known endemic area for Lassa fever – which was initially suspected as causing the outbreak.

From 22 September through 31 December 2018, a total of 146 suspected, 42 presumptive positive, and 32 confirmed cases, including 26 deaths (presumptive case fatality rate: 18%), have been reported across 15 of 18 Local Government Areas (LGAs) in Edo State (figure 1).

Blood specimens were obtained from 122 cases and sent for laboratory diagnosis; 42 (34%) samples were presumptive positive in-country based on IgM serology and sent to the regional reference laboratory, Institut Pasteur de Dakar (IPD), for confirmation. Thirty-two (76%) were confirmed by plaque reduction neutralization test (PRNT) or real-time polymerase chain reaction (RT-PCR). Males represent the majority of cases (108 of 146, 74%), and the most affected age group is 10–19 years with 48 cases (33%), followed by the age group 20–29 with 36 cases (25%). Initially, the affected LGAs were rural but since the end of November 2018, suspected cases have been reported from three urban LGAs. There has also been a report of two presumptive positive and one confirmed case in Oredo LGA, which includes the densely populated state capital Benin City, of about 1.5 million inhabitants.

At the time of the outbreak, population immunity in Edo State was very low, (based solely on routine immunisation administrative data, with vaccine coverage estimated at less than 50% in 2018). Edo State has just concluded a seven-day YF Reactive Vaccination Campaign implementation in 13 LGAs to rapidly boost population immunity and interrupt YF transmission. As of 31 December 2018, 1.47 million people have been vaccinated.

Entomological studies have revealed elevated indices of competent vectors, including Aedes aegypti, the mosquito species responsible for rapid amplification of arboviral disease in urban environments. Land-use practices, namely cultivation close to dwellings, may further exacerbate the spread of YF disease in this setting.

Since September 2017, when the Nigeria Centre for Disease Control (NCDC) informed WHO of a confirmed case of YF in Kwara State, Nigeria has been responding to successive YF outbreaks. The country officially notified WHO (via the International Health Regulations, 2005) on 15 September 2017. Since then, and as of 30 December 2018, 237 specimens tested IgM positive in-country. Eighty-two cases (including 13 deaths) were confirmed by IPD; these cases were reported from 27 LGAs in 14 States and have resulted in response campaigns in selected LGAs in six states.

The current outbreak of YF in Edo State in Nigeria is unusual in scale and severity, and the number of cases in time and place is very high in the context of the current national outbreak. The seasonal timing of the outbreak, in a period where many travellers enter the state from other states and countries for the holidays in December–January, adds to the risk for potential spread.

December 18, 2018

On 22 November 2018, the World Health Organization (WHO) was informed by Dutch authorities of a laboratory-confirmed case of yellow fever. The case-patient is a 26 year-old male who visited Gambia from 3 through 17 November 2018, with a three day trip to Senegal from 12 through 14 November. He had no history of vaccination for yellow fever prior to the trip.

On 18 November 2018, the case-patient developed symptoms including fever, nausea and vomiting. On19 November 2018 he was hospitalized with symptoms of acute liver failure and he is still in hospital as of 10 December.

The International Health Regulations National Focal Point (IHR NFP) from the Netherlands has notified counterparts in Gambia and Senegal about the case, and about the exact locations visited by the patient. There have been no other reports of confirmed yellow fever cases from Senegal, Gambia or The Netherlands at this time.

WHO risk assessment

Yellow fever is an acute viral illness that has the potential to spread rapidly and cause a serious public health impact in an unimmunized population. Vaccination is the most effective means of preventing the infection.

The importation of a case of yellow fever from Gambia or Senegal to the Netherlands represents international disease spread. However, sporadic imported cases of yellow fever from endemic countries in unvaccinated travellers are not unexpected. The risk of further local transmission of yellow fever virus related to this case in the Netherlands or further within the WHO European Region is currently considered to be negligible, as no competent vector for yellow fever has been established in the Netherlands. Both Senegal and Gambia have sustained high levels of population immunity against yellow fever, which should prevent major amplification of disease transmission in humans locally.

However, the high coverage in the endemic population will not offer protection to unimmunized individuals in high risk areas because yellow fever can be spread from the infected non-human primate reservoir to unimmunized persons through mosquito bites (vector-borne transmission). Therefore, travel to endemic areas remains a significant risk for unvaccinated individuals.

Mosquitoes are the world’s deadliest animals, killing thousands of people and causing millions of illnesses each year. To be able to reproduce and become effective disease carriers, mosquitoes must first attain optimal body size and nutritional status.

A pair of researchers at the University of California, Riverside, have succeeded in using CRISPR-Cas9, a powerful tool for altering DNA sequences and modifying gene function, to decrease mosquito body size, moving the research one step closer to eliminating mosquitoes that carry dengue fever and Zika virus.

Alexander Raikhel, a distinguished professor of entomology, and Lin Ling, a postdoctoral scholar working with Raikhel, used CRISPR-Cas9 to disrupt the serotonin receptor Aa5HT2B in Aedes aegypti mosquitoes, the vectors of dengue fever, yellow fever, and Zika virus.

“Aa5HT2B controls insulin-like peptides,” Raikhel said. “We were able to uncover the different roles that these peptides play in controlling body size and metabolism, and disrupt the gene associated with this receptor.”

“Mosquitoes of small size with diminished fat resources mature later and live shorter lives than nonmodified mosquitoes,” he said. “Thus, these genetically engineered mosquitoes have low reproductive capacity and ability to transmit disease pathogens. These features of CRISR-Cas9 mutant mosquitoes can be exploited for developing novel mosquito control approaches. Many challenges remain on the road, however, toward achieving this goal.”

French Guiana is a French overseas region bordering Brazil and Suriname. It is the only European territory geographically located in the Amazonian region, and considered endemic for yellow fever (YF). The confirmation of two human YF cases unusually close in time confirms that sylvatic YF circulation is currently occurring in this region.

In 2017, epizootics and sporadic human cases were observed in the northern part of the nearby state of Pará, Brazil; a recent case in neighbouring Suriname was identified in the Brokopondo lake area, less than 100 km away from its border with FG. These data suggest ongoing viral circulation in the wider Guiana Shield region. It is not clear, however, whether this is linked with the major epidemics recently observed in the south-eastern region of Brazil.

As the surrounding territories in the Amazonian region, FG is exposed to the risk of both sylvatic (observed) and urban (potential) YF. A sylvatic circulation of YF virus in FG was documented in 1994–95, in a study showing a seroprevalence of 26–35% among NHP in the Petit Saut lake dam forest, and was in favour of cyclic and recurrent epizootics. Aedes aegypti, an urban vector for YF virus, is largely present in FG. The last documented evidence of human epidemic transmission in an urban context in FG dates back to 1902.

Since 1967, YF vaccination has been compulsory for everyone above 1 year of age living in or travelling to FG (airport vaccination status controls are in place). The latest regional vaccination coverage estimates available for FG range from 80–90% to more than 95%. These figures are in line with the World Health Organization targets of a 60–80% immunisation coverage to avoid major YF epidemics, but are not fully satisfactory considering the regional 95% coverage target.

Vaccination coverage should be improved particularly in persons living and working in the forest, who are exposed during the day to sylvatic vectors. It should also be improved in migrants and other vulnerable populations who are more susceptible to being unvaccinated and live in densely populated urban areas (with a risk of urban local transmission), or participate to illegal activities in the forest (with a risk of sporadic cases or clusters in a sylvatic context). A recent random-sampling, whole-population survey will produce vaccination coverage estimates to assist health authorities in targeting at-risk populations.